Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia

The authors performed a genome-wide association study of single nucleotide polymorphisms (SNPs) in a discovery cohort with 2285 children with ALL, treated on the Children’s Oncology Group AALL0232 protocol. They found a SNP near the glutamate receptor GRIN3A locus (9q31.1) associated with higher risk of corticosteroid-induced osteonecrosis (hazard ratio = 2.03). In 2 different other cohorts this association was confirmed. The control cohorts included 361 children with ALL on St. Jude’s Total XV protocol and 309 non-ALL patients from Vanderbilt University’s BioVU repository treated with glucocorticoids. Multivariate analysis revealed age >10 y, and female gender to be associated with higher risk of osteonecrosis. In a meta-analysis osteonecrosis-associated glutamate receptor variants were also associated with other vascular phenotypes including cerebral ischemia and arterial embolism and thrombosis.